Summary The corticospinal tract is an important target for motor recovery after spinal cord injury (SCI) in animals and humans [1-5]. Voluntary motor output depends on the efficacy of synapses between corticospinal axons and spinal motoneurons, which can be modulated by the precise timing of neuronal spikes [6-8]. Using noninvasive techniques, we developed tailored protocols for precise timing of the arrival of descending and peripheral volleys at corticospinal-motoneuronal synapses of an intrinsic finger muscle in humans with chronic incomplete SCI. We found that arrival of presyn-aptic volleys prior to motoneuron discharge enhanced corticospinal transmission and hand voluntary motor output. The reverse order of volley arrival and sham stimulation did not affect or decreased voluntary motor output and electrophysiological outcomes. These findings are the first demonstration that spike timing-dependent plasticity of residual corticospinal-motoneuronal synapses provides a mechanism to improve motor function after SCI. Modulation of residual corticospinal-motoneuronal synapses may present a novel therapeutic target for enhancing voluntary motor output in motor disorders affecting the corticospinal tract.

Our findings suggest that muscle contraction during PCMS potentiates corticospinal transmission. PCMS applied during voluntary activity may represent a strategy to boost spinal plasticity after SCI.

Due to a production oversight, the version of this article originally published online on November 29, 2012 omitted several of the authors' proof corrections in the main text and Supplemental Information. Most importantly, in the statement ''The consistency between electrophysiological measurements across sessions, the use of a figure-of-eight coil in a lateromedial orientation to reliably elicit D waves (direct waves) [27, 28], and the specificity of our results support the view that human noninvasive electrophysiology can be successfully used to guide interventions after SCI'' in the second-to-last paragraph on page 4, the word ''lateromedial'' should have been changed to ''posteromedial.'' These errors do not affect the findings of the study and have now been corrected as intended both online and in print. The journal regrets the errors and apologizes to the authors for the inconvenience.